Pharmacology I - Injectable Anaesthetic Agents

Front 1

Increasing lipid solubility of injectable agents results has what affect on duration of action?

Back 1

makes it shorter acting

(because redistributed very easily, e.g. readily leaves circulation enters tissue)

Front 2

EFFECTOR SITE FOR INJECTABLE ANAESTHETICS IS ?

Back 2

the brain...this mean must cross BBB via circulatory system

Front 3

IDEAL INJECTABLE anaesthetic should hydrophilic or lipophilic?

Back 3

should be highly lipid solubility (cross membranes faster), but in water-soluble formation

Front 4

______ compounds cross blood brain barrier (BBB) faster

Back 4

smaller molecular weight

Front 5

Following IV administration, plasma concentration falls due to:
(2)

Back 5

1. Redistribution to….
vessel rich tissues
muscle
fat
2. Elimination
metabolism
excretion

* recovery seems to be predominantly due to redistribution

Front 6

distribution depends on what three things?

Back 6

organ perfusion
protein binding
lipid solubility

Front 7

Which route of administration usually yields more predictable effects, while allowing a lower dose to be used?

Back 7

Intravenous
* rapid onset
* lower dose
* predictable effect

Front 8

Which route of administration used for:
- slower onset
- higher dose in small volume
- less predictable effect
- no secure venous access
- must be non-irritant

Back 8

Intramuscular

Front 9

propofol, alfaxalone are examples of?

Back 9

STEROIDS

Front 10

Name the BARBITURATES (2)

Back 10

* thiopental
* phenobarbital

~ Pentobarbitone and methohexitone are no longer available as injectable drugs, so discussion will be restricted to mostly thiopental

Front 11

____ are almost insoluble in water and require complex vehicles to render them suitable for injection

Back 11

STEROIDS

Front 12

Name 2 DISSOCIATIVE AGENTS

Back 12

ketamine, tiletamine

Front 13

Name a IMIDAZOLE DERIVATIVE

Back 13

etomidate

Front 14

Long acting Barbiturate?

Back 14

Long duration of action -> PHENObarbital

Front 15

Ultra-short acting Barbiturate?

Back 15

THIOPENTAL
methohexitone~(no longer used as injectable)

Front 16

Formulation of Thiopentone is acidic or alkaline? ~pH?

Back 16

solution is very alkaline pH 10.5...but drug itself is a weak organic acid

Front 17

actual drug is a weak organic acid but it is prepared as a sodium salt buffered by sodium bicarbonate, mixed with anhydrous sodium carbonate to 5% (large animals only) or 2.5% solutions.

Back 17

Thiopentone

Front 18

Which of following can only be administered via IV? Why?
PROPOFOL THIOPENTAL ALFAXALONE KETAMINE ETOMIDATE

Back 18

THIOPENTAL
PROPOFOL
ETOMIDATE

Because painful irritants?
Ketamine is also painful injection but can be given IV, IM, SC,PO, maybe b/c has analgesic effects, very lipid soluble, and also partially water soluble

Front 19

Why is the fact that thiopental is highly alkaline (pH 10.5) significant?

Back 19

* concentrations greater than 2.5% are highly irritant to tissues

* pH of blood is 7.4 (less ionized at this pH)
* also PH MAKES IT BACTERCIDAL
* immiscible with acidic drugs; precipitation occurs

Front 20

Barbiturates interact with what receptor?

Back 20

GABA receptor; they are GABA'ergic....mimics GABA

Front 21

Which of following can be given IM?
PROPOFOL THIOPENTAL ALFAXALONE KETAMINE ETOMIDATE

Back 21

ALFAXALONE (IM or IV)
KETAMINE (IV, IM, SC,PO)

Front 22

Are GABA nt's (and barbiturates) inhibitory or excitatory in nature?

How so?

Back 22

inhibitory neurotransmitter

open Cl- channel allowing it to rush and hyperpolarize membrane...inhibiting neuronal depolarization...

Front 23

Which is more lipid soluble thiopental or ketamine?

Back 23

Ketamine 5X more lipid soluble than thiopental!
Ketamine is also partially water soluble so will have effect when
administered IV, IM, PO

Front 24

Is thiopental lipid soluble? how does this affect duration of action?

recovery of consciousness is primarily a function of?

Back 24

yes very lipid soluble, so short induction, also very short duration of action

recovery of consciousness is by redistribution
(not elimination, b/c metabolized slowly)

Front 25

is thiopental protein bound?

Back 25

yes

Front 26

How long can a freshly prepared bottle of thiopentone be stored?

Back 26

7 hours

Front 27

Is the ideal anesthetic agent long or short acting?

which barbiturate drug makes better injectable agent for surgery?

Back 27

short acting, can be readily adjusted by changing the administration rate

thiopental

Front 28

Is the ideal anticonvulsant drug long or short acting? (common sense)

which barbiturate drug makes better anticonvulsant drug?

Back 28

long acting...stopping convulsions for 30 seconds isn't going to do a whole lot of good

phenobarbital

Front 29

Cardiocasular effects of thiopentone?

Back 29

* vasodilation (mediated via depression of the medullary vasomotor centre)
* hypotension
* decr. vasculation resistance
* decr. CO

Front 30

Is thiopentone an analgesic?

intracranial affects?

Back 30

NO

depresses cerebral oxygen consumption (CMRO2) and intracranial pressure (ICP)

Front 31

Respiratory effects of thiopentone?

Due to reduced sensitivity of ____?

Back 31

• Respiratory depression - of both rate and tidal volume.

due to reduced sensitivity of the respiratory center to CO2

Front 32

Disadvantages of thiopentone?

Back 32

* CUMULATIVE – Accumulates after repeated doses; prolong recovery (so giving via CRI not good idea)
* hyperalgesic
* tissue irritation and sloughing on perivascular injection
* solutions don’t mix with other drugs (esp. acidic drugs)

Front 33

Give me names of 2 Injectable Anesthetics-Steroids!

Back 33

Propofol
Alfaxalone (Alfaxan-CD)(Saffan is old formulation, w/different vehicle; no longer licensed)

Front 34

Speed of onset of propofol=


Speed of onset of alfaxolone=

Back 34

60-90 seconds

• Relatively rapid onset of anaesthesia. Slower onset than propofol;
advised to administer for +60 seconds, to optimize predictable uptake into target tissue (brain), and thus achieve general anaesthesia using the minimum dose.

Front 35

Is alfaxalone considered ‘safer’ for hypoalbuminaemic patients than propofol?

Why?

Back 35

• 30-50% protein bound: ‘moderately’ protein bound so considered ‘safer’ for hypoalbuminaemic patients

* in contrast, propofol is 98% protein bound!

Front 36

Don’t use _____ in sight hounds (Greyhounds, Whippets, and Afghans etc.)


Also slow recovery in ______.

Back 36

Don’t use thiopentone in sight hounds

genetic hepatic metabolic defect in first step of hepatic metabolism

Also slow recovery in thin animals

Front 37

Can alfaxolone be administered via CRI? If not, why?

Back 37

alfaxolone is relatively non- cumulative so can be administered as a controlled rate infusion

also TIVA, IV, IM (IM administration requires large volumes)

Front 38

. Principal mechanism of recovery following induction of alfaxalone= ?

What else can you say about the recovery process?

Back 38

• Rapid recovery through redistribution and rapid metabolism
• -> recovery can sometimes psychomotor excitement w/hypersensitivity to stimuli, paddling and muscle tremors

Front 39

Contraindications of Propofol

Back 39

Cats-deficiency in glucuronide synthetase enzyme; hypoalbuminemic patients (b/c 98% protein bound!!!)

Also cats have poor capacity for triglyceride metabolism in general
VERY slow to recover, esp. from CRI

Front 40

Contraindications of alfaxalone

Back 40

Contraindicated in cats

occasional anaphylactoid reactions in cats - swollen pads

Also cats have poor capacity for triglyceride metabolism in general

Front 41

Propofol and Alfaxalone are agonist of ____?

Back 41

GABA agonists

Front 42

What steroid is NMDA/glutamate/glycine antagonist??

Back 42

Propofol, but it's GABA agonist

Front 43

CNS effects of alfaxolone?

How does it act?
Analgesic effects?

Back 43

• Alfaxalone is a neuroactive steroid; acts on chloride ion transport by binding to central GABA-A receptors.
• NO analgesic activity; use w/analgesic premed for surgical interventions.

Front 44

Which of following causes LEAST respiratory depression?
A. thiopental
B. alfaxolone
C. propofol

Back 44

B. alfaxolone

less respiratory depression than thio/ propofol

Front 45

Which of following is good muscle relaxant?
A. thiopental
B. alfaxolone
C. propofol

Back 45

B. alfaxolone
C. propofol

Front 46

Name Imidazole derivative

Back 46

• Etomidate

Front 47

Mechanism of action of ETOMIDATE anesthesia? Similar to what?? Depressed what?
Agonist of?

Back 47

ETOMIDATE = GABA’ergic: mode of anaesthetic action is similar to PROPOFOL
also depresses RAS

Front 48

Effects of Etomidate on CNS and cranium?

Back 48

* depresses RAS like propofol
* like all most injectables decreases intracranial pressure
* reduces cerebral blood flow while maintaining mean arterial BP, so that cerebral perfusion pressure is maintained
* Myoclonus (invol. muscle twitching)

Front 49

Rarely if ever administered alone, Ketamine is commonly used in combination with _____?

Back 49

benzodiazepines, ACP and a2 agonists.

Front 50

True or false:
Both Propofol and Alfaxalone are characterized by rapid induction and rapid metabolism?

Back 50

• TRUE

FYI: But recovery from Alfaxalone can sometimes involve psychomotor excitement w/hypersensitivity to stimuli, paddling and muscle tremors

Front 51

What are some adverse effects of etomidate in animals? Are these effects clinically significant?

Other adverse effects?

Back 51

Temporary suppression of ADRENOCORTICAL function
Significant inhibition of adrenal synthesis of cortisol, aldosterone, and corticosterone
(But effects usually short-lived; only significant in animal with adrenal insufficiency)

Like propoforol, causes pain on injection..can reduce this by injecting a low dose of dilute lidocaine immediately beforehand.

Front 52

Which drug is recommended to use heavy sedation prior to induction, or co-administer with benzodiazepine or opioid and is generally reserved for use in high-risk patients?

Back 52

Etomidate

Front 53

1. What are cardiovascular effects of ETOMIDATE?


2. What are cardiovascular effects of propofol and thiopental?

Back 53

1. In contrast to other injectable agents, etomidate has minimal effects on cardiovascular ****

2. propofol and thiopental both cause vasodilation, decr. CO, decreased vascular resistance

Front 54

When would Intraperitoneal agents be approriate?

Back 54

small furries with tiny veins

Front 55

Which Injectable agent does following refer?
* clearance of _____ exceeds hepatic blood flow - are additional extrahepatic metabolic pathways–
pulm., renal, sm.intestine
• Recovery smooth and rapid (excepting cats), w/in 5-8 min.
• No ‘hangover’ after awaken

Back 55

PROPOFOL

* alters mood less (less negatively?) than thio and promotes feeling of well being by increasing dopamine levels
* awaken contented and "amorous"

Front 56

Aside from making patients feel contented, what are CNS effects of PROPOFOL?

Back 56

• enhances GABA activity (hypnosis)
• inhibits NMDA activity
• NO effect on pain perception
• Reduces cerebral metabolic oxygen requirement (CMRO2)
• reduces pressure
• strong anti-convulsant & anti-emetic effects

Front 57

Where does name for dissociative drugs come from?

Are KETAMINE & TILETAMINE good muscle relaxants?

Back 57

Humans feel "dissociated", hypnotic/cataleptic (muscle rigidity) effects in animals

NO, ketamine incr. muscular tone, and tiletamine can cause spasms; that is why rarely used alone

Front 58

Which Injectable agent does following refer?
Wide safety margin. Acute tolerance studies showed that with ventilatory support, dogs survived 10X clinically effective dose of ____, cats 5X clinically effective dose.

Back 58

Alfaxalone (alfaxan-CD)

Front 59

What drug has similar CNS, cardiovascular, and respiratory effects to ketamine and maintains good CV and respiratory function?

Back 59

Telazol (Tiletamine/Zolazepam)

Front 60

Which Injectable agent matches this description/indication?
Routes of administration of _____= effective when administered IV OR IM and so used for darting wild animals and IM induction of feral cats, aggressive dogs.
• In wild animals and certain domestic species, it is typically administered IM without prior premedication

Back 60

TELAZOL: TILETAMINE/ZOLAZEPAM

Front 61

Onset of ETOMIDATE?

Back 61

• Very rapid onset – highly lipid soluble, large un-ionised fraction at pH 7.4
• Rapidly penetrates BBB, unconsciousness within one arm-brain time (60-90 sec), similar to propofol

Front 62

Recovery of ETOMIDATE is predominantly due to ?

elimination half-life is long or short? what route of administration?

Back 62

redistribution

relatively short elimination half-life and rapid clearance...suitable for CRI or single injection

Front 63

How does rate of biotransformation of etomidate compare to thiopental?
is metabolite active?

Is etomidate protein bound?

Back 63

five times faster than thiopental; metabolite is not active

yes, highly protein bound

Front 64

Is ketamine a good choice for anaesthesia for head trauma or neurosurgery patients?

Is ketamine a good choice for glaucoma patients?

Back 64

No, bad choice - because ketamine increases intracranial pressure

Do not use in glaucoma patients, increases intra-ocular pressure

Front 65

Does ketamine need to be used in combination with another drug with muscle relaxant properties?

Back 65

Yes

Front 66

What dissociative agents primary site of "anesthetic" action is the thalamoneocortical projection system, increases salivation and has NMDA receptor antagonism and effects on non-NMDA glutamate receptors?

Back 66

Ketamine

Front 67

Which of following do NOT have rapid elimination?
PROPOFOL THIOPENTAL ALFAXALONE KETAMINE ETOMIDATE

Back 67

THIOPENTAL
KETAMINE: prolonged after multiple top-ups

Front 68

Which injectable anasthetic agent forms active metabolite in liver?
What kind of metabolism? Name of metabolite?

Back 68

Ketamine is metabolized in the liver by demethylation (cytochrome p450 system) into nor-ketamine (active metabolite) !!!

Front 69

What are some of the cardiovascular effects of ketamine?

Back 69

Unlike other injectable - stimulates CVS, INCREASES BP, CO & HR
This Increases myocardial work; overrides myocardial depressant effects
May put unwanted stress on a diseased CV system
(Do not use in congestive heart failure or animals with severe hypertension)

Front 70

What are some advantages of "S" ketamine?

Back 70

Less adverse side effects
4 times more potent

Front 71

Why does 10% ketamine sting when injected?

Back 71

pH 3.5

Front 72

What are some contraindications of ketamine?

Back 72

Head trauma or neurosurgery patients
Increases intraocular pressure (glaucoma)
Certain cardiovascular disease
hepatic or renal disease o urinary obstruction
Animals at risk of seizuring

Front 73

Solvent in which alfaxalone supplied (as Alfaxan-CD)?

Back 73

• Alfaxalone is solubilised in CYCLODEXTRIN
(non-toxic polysaccharide solubilising agent which does not stimulate histamine release as predecessor 'Saffan' did)

Front 74

Which Injectable agent does following refer?
The mixture standardly contains NO preservatives and thus is a perfect medium for bacterial growth.
For this reason ____ must be discarded after 12 - 24 hours/ at the end of the day, CERTAINLY NOT stored at room temperature and re-used.

Back 74

PROPOFOL

prepared as a 1% or 2% emulsion in 10% soybean oil, 2.25% glycerol, 1.2% purified EGG phosphatide at pH 7

Front 75

____ is a chiral molecule; how so?

Back 75

ketamine;

standard commercial preparation is a racemic mixture of S (+) and R (-) ISOMERS

Front 76

This drug causes "functional disorganization" of the thalamus and the limbic cortex
• also blocks transmission of impulses in the medial reticular formation, which transmits the affective emotional components of nociception from spinal cord to higher centres

Back 76

Ketamine

What other inj. agents affect RAS?

Front 77

Zolazepam is a _____(enter drug class), contributing sedation, hypnosis, muscle relaxation, anxiolysis, and sedation

Back 77

benzodiazepine

Front 78

Behavioral effects common during recovery from TILETAMINE/ ZOLAZEPAM anaesthsia:
In dogs and cats?

Back 78

In dogs and cats, recoveries are typically prolonged and rough, with the possibility of convulsions.

Front 79

True or False: Telazol can cause these adverse effects?
• Causes salivation
• Causes muscular spasms and poor muscle relaxation for surgery
• Can vomiting
• Causes unpleasant emergence reactions
• Induces tachycardia and hypertension

Back 79

True

Front 80

Telazol/ Zoletil combined with an α2 agonist (typically xylazine) is an effective, potent and popular anaesthetic in ___.

Back 80

pigs

Front 81

Which drug wears off first in cats: TILETAMINE or ZOLAZEPAM?

Back 81

In cats, Zolazepam outlasts tiletamine.

Front 82

Which drug wears off first in dogs: TILETAMINE or ZOLAZEPAM?

Back 82

In dogs, TILETAMINE’s effects outlast zolazepam’s and so recovery is prolonged, violent, noisy, etc.

Front 83

Contraindications to Zoletil?

Back 83

> Identical to ketamine

• Associated with severe cardiac or respiratory decompensation in compromised animals
• AVOID in animals with pancreatic deficiency, severe renal or hepatic dysfunction